Computational Models of Descending Pain Regulatory Networks in Chronic Pain

四分之一的人在一生中遭受慢性疼痛，慢性疼痛是一个全球性的问题。为了理解慢性化的过程，开发更好的相关系统的计算模型对于治疗的持续进展至关重要。急性和慢性疼痛感知的一个关键特征是下行调节网络对上行伤害性通路的调节。这些下行回路在慢性疼痛患者中变得功能障碍，先前的神经生理学证据表明它们的功能障碍可能是由于脑干核和延髓头端腹侧的皮质控制中断。有明确的神经生理学特征标志着他们的正确和功能失调的行为，以及从其他实验室收集的啮齿动物数据。然而，目前还没有下行疼痛网络的计算模型，因此尚不清楚它们为什么会功能失调。因此，根据EPSRC医疗保健技术主题，我将使用控制理论来开发这些网络的计算模型。然后，我将通过将上行-下行通路视为闭环控制系统来模拟它们的功能障碍，以了解它们在慢性疼痛中功能障碍的原因。这项研究的意义可以为疼痛的药理学治疗提供目标，计算模型将提供对这些回路行为的预测，然后可以成为进一步实验和药理学研究的途径。

With one in four people suffering from chronic pain in their lifetime, chronic pain is a global concern. Developing better computational models of the systems involved, in order to understand the processes of chronification, is vital for continued progress towards treatment. One key feature of acute and chronic pain perception is the modulation of ascending nociceptive pathways by descending regulatory networks. These descending circuits become dysfunctional in patients with chronic pain, with previous neurophysiological evidence suggesting their dysfunction may be due to disrupted cortical control of brainstem nuclei and rostral ventral medulla. There are clear neurophysiological features that mark their correct and dysfunctional behaviour, alongside data collected in rodents from other labs. However, computational models of descending pain networks are currently absent, and thus it is not clear why they become dysfunctional. Therefore, in line with the EPSRC Healthcare Technologies theme, I will use control theory to develop a computational model of these networks. I will then simulate their dysfunction by treating the ascending-descending pathways as a closed-loop control system to understand why they are dysfunctional in chronic pain. The implications of this research could provide targets for the pharmacological treatment of pain, and a computational model would provide predictions about the behaviour of these circuits, which could then become avenues for further experimental and pharmacological research.